L1 elements constitute the largest and most widely distributed family of self-replicating elements in the mammalian genome. L1s affect many aspects of genome structure, and are a major source of mutations, both directly and indirectly. The selfish parasitic model explains persistence of transposable elements as genomic invaders whose sole function is to replicate themselves, at the expense of their host. Observations in mice are somewhat unexpected from this perspective, in that most copies of L1s in the genome are incapable of transposition, and the few active elements belong to one or two "master" lineages. If L1s are truly selfish, it is not clear why there has not been a proliferation of active lineages, rather than a steady state of one or a few lineages. What variables constrain L1s to a small number of lineages yet assure that these L1s do not become extinct? To address this question it is critical to have access to a large number of closely related species and natural, non-inbred populations, making Peromyscus the model system of choice. The objectives of this proposal are 1) to determine the magnitude and causes of L1 sequence variation in deer mice, Peromyscus, to evaluate the master lineage paradigm; and 2) to assess L1 variation and genome structure in rice rats, Oryzomys, in which L1 elements appear to be extinct. The long term goal of this research is to understand how selection acting at the level of the element and/or host maintains L1s in the genome while constraining both the number and activity of master elements.